Venous thromboembolism in myelodysplastic syndrome patients receiving lenalidomide: results from postmarketing surveillance and data mining techniques.

BACKGROUND AND OBJECTIVES: Multiple myeloma treatment with lenalidomide-based regimens is associated with risk of venous thromboembolism (VTE), particularly during concomitant use with erythropoiesis-stimulating agents (ESAs). The risk of VTE in myelodysplastic syndrome (MDS) patients treated with lenalidomide is not well characterized and the background risk in untreated patients is not known. This study set out to determine the reporting rate of VTE in MDS patients on lenalidomide in the two years of postmarketing experience in the US, and to investigate whether there is a disproportional signal of VTE in MDS patients on lenalidomide by screening the US FDA Adverse Event Reporting System (AERS) safety database. METHODS: The MDS population exposed to lenalidomide was obtained from RevAssist, the company's proprietary restrictive distribution programme. VTE reports were identified from the company's postmarketing surveillance safety database. The FDA AERS database was used for disproportionality analysis, and signal scores computed using three algorithms: multi-item gamma Poisson shrinker (MGPS), proportional reporting ratio (PRR), and reporting odds ratios (ROR). RESULTS: A total of 7764 MDS patients were prescribed lenalidomide during the first two years of commercial use in the US. VTE representing deep vein thrombosis and pulmonary embolism was reported in 41 patients, a reporting rate of 0.53%. The computed signal scores did not exceed the statistical threshold for identification of a significant disproportional signal for VTE in MDS reports involving use of lenalidomide without concomitant use of ESAs. However, a disproportional signal of VTE was detected in MDS reports where lenalidomide was concurrently used with ESAs. CONCLUSION: The VTE reporting rate for MDS patients receiving lenalidomide during the first two years of postmarketing exposure was low (0.53%). Disproportionality analysis demonstrated a statistically meaningful association of VTE with lenalidomide concomitantly used with ESAs in MDS patients, but the association was not statistically significant when lenalidomide was used in the absence of ESAs.

Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

BACKGROUND: This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. METHODS: Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. RESULTS: Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. CONCLUSIONS: There are consistent and substantial differences between atypical antipsychotic drugs in the disproportionality reporting ratios relating to glycemic effects, especially life-threatening events, in the AERS database. The relative associational rankings of drugs are similar in reports from younger and older patients. These results agree with several other reports in the literature, do not support a "class effect" hypothesis, and provide a strong rationale for further studies to clarify the issue.

Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data.

BACKGROUND: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. OBJECTIVE: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. METHODS: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving > or =1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting beta(2)-agonist (SABA), or long-acting beta(2)-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. RESULTS: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. CONCLUSIONS: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and beta(2)-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.